chr2-71070826-C-A

Variant names:

• chr2-71070826-C-A
• rs553026134
• NM_017567.6:c.200C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017567.6(NAGK):​c.200C>A​(p.Pro67Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NAGK NM_017567.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

Genes affected

NAGK (HGNC:17174): (N-acetylglucosamine kinase) This gene encodes a member of the N-acetylhexosamine kinase family. The encoded protein catalyzes the conversion of N-acetyl-D-glucosamine to N-acetyl-D-glucosamine 6-phosphate, and is the major mammalian enzyme which recovers amino sugars. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017567.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	NM_017567.6	MANE Select	c.200C>A	p.Pro67Gln	missense	Exon 3 of 10	NP_060037.4
	NAGK	NM_001330425.3		c.47C>A	p.Pro16Gln	missense	Exon 2 of 9	NP_001317354.1	C9JEV6
	NAGK	NM_001330426.2		c.47C>A	p.Pro16Gln	missense	Exon 3 of 10	NP_001317355.1	C9JEV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAGK	ENST00000244204.11	TSL:1 MANE Select	c.200C>A	p.Pro67Gln	missense	Exon 3 of 10	ENSP00000244204.5	Q9UJ70-1
	NAGK	ENST00000455662.6	TSL:1	c.338C>A	p.Pro113Gln	missense	Exon 3 of 10	ENSP00000389087.2	Q9UJ70-2
	NAGK	ENST00000613852.4	TSL:1	c.338C>A	p.Pro113Gln	missense	Exon 3 of 10	ENSP00000477639.1	Q9UJ70-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.22
Sift	Benign	0.18	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.70		Loss of loop (P = 0.0128)
MVP		0.55
MPC		0.33
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.61
gMVP		0.70
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs553026134; hg19: chr2-71297956;